Project Summary There are up to 300,000 cases of Lyme disease each year in the U.S., often affecting children. Between 10- 15% of children with Lyme disease develop meningitis. Current guidelines recommend treatment of Lyme meningitis with two weeks of intravenous antibiotics, requiring a catheter to be inserted in the child's arm for a prolonged period of time. This can cause anxiety and discomfort for the child and is costly. One out of six children also develops complications from the catheter such as blockage, blood clots, or infection. An oral alternative, doxycycline is available in children 8-17 years old. The objective of this study is to compare use of oral doxycycline to intravenous ceftriaxone. If oral doxycycline treats short and long-term symptoms of Lyme meningitis equally as well as intravenous ceftriaxone with lower rates of side effects, then oral doxycycline could be used to treat all children with Lyme meningitis. The trial will enroll 380 children in a network of pediatric hospitals in regions of the U.S. where Lyme disease is found. Children will be randomized to either receive two weeks of oral doxycycline or intravenous ceftriaxone. Investigators will measure daily symptoms of Lyme meningitis such as headache, neck pain or facial palsy until they resolve. The investigators will also measure complications of treatment such as allergic reactions, catheter problems, and secondary infections. Finally, the investigators will compare the quality of life six months after treatment in the two treatment arms of the study. This will be the first comparative effectiveness trial of oral doxycycline versus intravenous ceftriaxone in children in the U.S. with Lyme meningitis. Success would improve the care of these children by providing an equally effective oral treatment that would lower complication rates, increase patient satisfaction, and reduce health care costs. During the time period covered by this grant, a team of experts including pediatricians, infectious disease doctors, neurologists, and statisticians will plan the clinical trial. The investigators will coordinate study planning activities with the Advance Clinical and Translational Research Center in Rhode Island, and Pedi Lyme Net which is a network of pediatric hospitals that identify children for Lyme disease research. The specific aims of this trial planning grant are: 1) To finalize the logistical planning for the trial and 2) To finalize the development of materials for the trial. Logistical planning will include recruiting additional enrollment sites to Pedi Lyme Net, auditing sites to determine resource needs, obtaining regulatory approval of the IRBs and FDA, creating of a trial budget and timeline, and developing a per-enrollment reimbursement model. Materials to be developed will include manual of procedures, recruitment and informed consent documents, data collection forms, and training materials.